This study will facilitate the development of the next generation of potent and selective inhibitors of the NSD histone methyltransferases.Increasing nitrogen use efficiency (NUE) is critical to improve crop yield, reduce N fertilizer demand and alleviate environmental pollution. N remobilization is a key component of NUE. The nitrate transporter NRT1.7 is responsible for loading excess nitrate stored in source leaves into phloem and facilitates nitrate allocation to sink leaves. Under N starvation, the nrt1.7 mutant exhibits growth retardation, indicating that NRT1.7-mediated source-to-sink remobilization of stored nitrate is important for sustaining growth in plants. To energize NRT1.7-mediated nitrate recycling, we introduced a hyperactive chimeric nitrate transporter NC4N driven by the NRT1.7 promoter into the nrt1.7 mutant. NRT1.7pNC4N3' transgenic plants accumulated more nitrate in younger leaves, and 15NO3- tracing analysis revealed that more 15N was remobilized into sink tissues. Consistently, transgenic Arabidopsis, tobacco and rice plants showed improved growth or yield. Our study suggests that enhancing source-to-sink nitrate remobilization represents a new strategy for enhancing NUE and crop production.Foxtail millet (Setaria italica) is an important crop species and an emerging model plant for C4 grasses. However, functional genomics research on foxtail millet is challenging because of its long generation time, relatively large stature and recalcitrance to genetic transformation. Here we report the development of xiaomi, a rapid-cycling mini foxtail millet mutant as a C4 model system. Five to six generations of xiaomi can be grown in a year in growth chambers due to its short life cycle and small plant size, similar to Arabidopsis. A point mutation in the Phytochrome C (PHYC) gene was found to be causal for these characteristics. PHYC encodes a light receptor essential for photoperiodic flowering. A reference-grade xiaomi genome comprising 429.94?Mb of sequence was assembled and a gene-expression atlas from 11 different tissues was developed. https://www.selleckchem.com/products/ew-7197.html These resources, together with an established highly efficient transformation system and a multi-omics database, make xiaomi an ideal model system for functional studies of C4 plants.Diel and seasonal oscillations are two major environmental changes in nature. While organisms cope with the former by the well-characterized mechanism of the circadian clock1,2, there is limited information on the molecular mechanisms underlying long-term responses to the latter3-5. Histone H3 lysine 27 trimethylation (H3K27me3), a repressive histone modification, imparts stability and plasticity to gene regulation during developmental transitions6-9. Here we studied the seasonal and diel dynamics of H3K27me3 at the genome-wide level in a natural population of perennial Arabidopsis halleri and compared these dynamics with those of histone H3 lysine 4 trimethylation (H3K4me3), an active histone modification. Chromatin immunoprecipitation sequencing revealed that H3K27me3 exhibits seasonal plasticity and diel stability. Furthermore, we found that the seasonal H3K27me3 oscillation is delayed in phase relative to the H3K4me3 oscillation, particularly for genes associated with environmental memory. Our findings suggest that H3K27me3 monitors past transcriptional activity to create long-term gene expression trends during organismal responses over weeks in natural fluctuating environments.Rubisco sustains the biosphere through the fixation of CO2 into biomass. In plants and cyanobacteria, form I Rubisco is structurally comprised of large and small subunits, whereas all other Rubisco forms lack small subunits. The rise of the form I complex through the innovation of small subunits represents a key, yet poorly understood, transition in Rubisco's evolution. Through metagenomic analyses, we discovered a previously uncharacterized clade sister to form I Rubisco that evolved without small subunits. This clade diverged before the evolution of cyanobacteria and the origin of the small subunit; thus, it provides a unique reference point to advance our understanding of form I Rubisco evolution. Structural and kinetic data presented here reveal how a proto-form I Rubisco assembled and functioned without the structural stability imparted from small subunits. Our findings provide insight into a key evolutionary transition of the most abundant enzyme on Earth and the predominant entry point for nearly all global organic carbon.Drug candidates that form covalent linkages with their target proteins have been underexplored compared with the conventional counterparts that modulate biological function by reversibly binding to proteins, in part due to concerns about off-target reactivity. However, toxicity linked to off-target reactivity can be minimized by using latent electrophiles that only become activated towards covalent bond formation on binding a specific protein. Here we study sulfuramidimidoyl fluorides, a class of weak electrophiles that undergo sulfur(VI) fluoride exchange chemistry. We show that equilibrium binding of a sulfuramidimidoyl fluoride to a protein can allow nucleophilic attack by a specific amino acid side chain, which leads to conjugate formation. We incubated small molecules, each bearing a sulfuramidimidoyl fluoride electrophile, with human cell lysate, and the protein conjugates formed were identified by affinity chromatography-mass spectrometry. This inverse drug discovery approach identified a compound that covalently binds to and irreversibly inhibits the activity of poly(ADP-ribose) polymerase 1, an important anticancer target in living cells.Environments furnish multiple information sources for making predictions about future events. Here we use behavioural modelling and functional magnetic resonance imaging to describe how humans select predictors that might be most relevant. First, during early encounters with potential predictors, participants' selections were explorative and directed towards subjectively uncertain predictors (positive uncertainty effect). This was particularly the case when many future opportunities remained to exploit knowledge gained. Then, preferences for accurate predictors increased over time, while uncertain predictors were avoided (negative uncertainty effect). The behavioural transition from positive to negative uncertainty-driven selections was accompanied by changes in the representations of belief uncertainty in ventromedial prefrontal cortex (vmPFC). The polarity of uncertainty representations (positive or negative encoding of uncertainty) changed between exploration and exploitation periods. Moreover, the two periods were separated by a third transitional period in which beliefs about predictors' accuracy predominated.